Patch and method for producing the same

Abstract

A method for producing a patch comprising a support layer and an adhesive agent layer comprises: a mixture preparation step of mixing asenapine or a pharmaceutically acceptable salt thereof with sodium acetate whose particle diameter D 50 at a cumulative volume of 50% in a particle diameter distribution is 40 to 1000 μm, in such a manner that the sodium acetate and sodium diacetate generated from the sodium acetate have a particle diameter D 50 of 10 μm or smaller, thereby obtaining a mixture containing the sodium diacetate and the asenapine or pharmaceutically acceptable salt; and an adhesive-agent-layer formation step of forming the adhesive agent layer comprising the sodium diacetate, the asenapine or pharmaceutically acceptable salt, and a pressure-sensitive adhesive base agent, by using an adhesive agent layer composition obtained by mixing the mixture with the pressure-sensitive adhesive base agent.

The invention claimed is: 
     
       1. A patch for administering asenapine, comprising:
 a support layer; and 
 an adhesive agent layer formed on the support layer and comprising sodium diacetate, a pressure-sensitive adhesive base agent, and at least one of asenapine and asenapine maleate, 
 wherein the sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or asenapine maleate, the sodium diacetate has a particle diameter D 50  of 10 μm or smaller, the asenapine and/or asenapine maleate has a content in terms of free asenapine in a range of 1% to 15% relative to the adhesive agent layer, a mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.5 to 1:4, the adhesive agent layer measured by X-ray diffraction has a peak intensity from the sodium diacetate which is higher than a peak intensity from sodium acetate, and when a content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC 2-120  of free asenapine for a period starting from the time when the patch is brought into contact with skin for 24 hours is 8,077 pg·hr/mL or more. 
 
     
     
       2. The patch according to  claim 1 , wherein the adhesive agent layer comprises the asenapine maleate. 
     
     
       3. The patch according to  claim 1 , wherein the adhesive agent layer further comprises an absorption enhancer. 
     
     
       4. The patch according to  claim 3 , wherein a mass ratio of the asenapine and/or asenapine maleate to the absorption enhancer where a mass of the asenapine and/or asenapine maleate is in terms of free asenapine is in a range of 1:0.1 to 1:10. 
     
     
       5. The patch according to  claim 1 , wherein the content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is in a range of 1.5% to 12% relative to the adhesive agent layer. 
     
     
       6. The patch according to  claim 1 , wherein an AUC 2-120  of an asenapine metabolite is 20% or less of the AUC 2-120  of the free asenapine. 
     
     
       7. The patch according to  claim 2 , wherein an AUC 2-120  of an asenapine metabolite is 20% or less of an AUC 2-120  of free asenapine. 
     
     
       8. The patch according to  claim 1 , wherein the sodium diacetate has a content in a range of 0.3% to 10% or less relative to the adhesive agent layer. 
     
     
       9. The patch according to  claim 1 , wherein the sodium diacetate has a content in a range of 0.5% to 6% or less relative to the adhesive agent layer. 
     
     
       10. The patch according to  claim 5 , wherein the sodium diacetate has a content in a range of 0.3% to 10% or less relative to the adhesive agent layer. 
     
     
       11. The patch according to  claim 5 , wherein the sodium diacetate has a content in a range of 0.5% to 6% or less relative to the adhesive agent layer. 
     
     
       12. The patch according to  claim 1 , wherein the mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.75 to 1:2. 
     
     
       13. The patch according to  claim 12 , wherein the sodium acetate has a content of 10% or less relative to the adhesive agent layer. 
     
     
       14. The patch according to  claim 12 , wherein the sodium acetate has a content of 5% or less relative to the adhesive agent layer. 
     
     
       15. A method for treating a central nervous system disease, comprising:
 administering asenapine to a patient in need thereof by applying, on a skin of the patient, a patch comprising a support layer, and an adhesive agent layer formed on the support layer and comprising sodium diacetate, a pressure-sensitive adhesive base agent, and at least one of asenapine and asenapine maleate such that when a content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC 2-120  of free asenapine for a period starting from the time when the patch is brought into contact with the skin for 24 hours is 8,077 pg·hr/mL or more, 
 wherein the sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or asenapine maleate, the sodium diacetate has a particle diameter IC 50  of 10 μm or smaller, the asenapine and/or asenapine maleate has a content in terms of free asenapine in a range of 1% to 15% relative to the adhesive agent layer, a mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.5 to 1:4, and the adhesive agent layer measured by X-ray diffraction has a peak intensity from the sodium diacetate which is higher than a peak intensity from sodium acetate. 
 
     
     
       16. The method of  claim 15 , wherein an AUC 2-120  of an asenapine metabolite is 20% or less of the AUC 2-120  of the free asenapine. 
     
     
       17. The method of  claim 15 , wherein the adhesive agent layer comprises the asenapine maleate. 
     
     
       18. The method of  claim 15 , wherein the adhesive agent layer further comprises an absorption enhancer. 
     
     
       19. The method of  claim 15 , wherein the central nervous system disease is schizophrenia. 
     
     
       20. The method of  claim 15 , wherein the mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.75 to 1:2.